1. Field of the Invention
This invention relates generally to a catalytic conformational sensor method and application of such method for detecting proteins and proteinaceous particles; and more particularly to detecting misfolded or disease-associated proteins and proteinaceous particles.
2. Related Art
The present invention is not limited to the detection of proteins or peptides in infectious samples. It also includes detection of proteinaceous particles such as prions. Prions are small proteinaceous particles with no nucleic acids, thus are resistant to most nucleic-acid modifying procedures and proteases. They are infectious particles that play key roles in the transmission of several diseases such as Creutzfeldt-Jakob syndrome, transmissible spongiform encephalopathy (TSE), and scrapie a neurological disorder in sheep and goats.1 Diseases caused by prions can be hard to diagnose since the disease may be latent where the infection is dormant, or may be subclinical where abnormal prion is demonstrable but the disease remains an acute or chronic symptomless infection. Moreover, normal homologues of a prion-associated protein exist in the brains of uninfected organisms, further complicating detection.2 Prions associate with a protein referred to as PrP 27-30, a 28 kdalton hydrophobic glycoprotein, that polymerizes (aggregates) into rod-like filaments, plaques of which are found in infected brains. The normal protein homologue differs from prions in that it is readily degradable as opposed to prions which are highly resistant to proteases. Some theorists believe that prions may contain extremely small amounts of highly infectious nucleic acid, undetectable by conventional assay methods.3 As a result, many current techniques used to detect the presence of prion-related infections rely on the gross morphology changes in the brain and immunochemistry techniques that are generally applied only after symptoms have already manifest themselves. 1 Clayton Thomas, Tabor's Cyclopedic Medical Dictionary (Phil., F.A. Davis Company, 1989), at 1485.2 Ivan Roitt, et al., Immunology (Mosby-Year Book Europe Limited, 1993), at 15.1.3 Benjamin Lewin, Genes IV (Oxford Univ. Press, New York, 1990), at 108.
The following is an evaluation of current detection methods.
                Brain Tissue Sampling. Cross-sections of brain can be used to examine and monitor gross morphology changes indicative of disease states such as the appearance of spongiform in the brain, in addition to immunohistochemistry techniques such as antibody-based assays or affinity chromatography which can detect disease-specific prion deposits. These techniques are used for a conclusive bovine spongiform encephalopathy (BSE) diagnosis after slaughter of animals displaying clinical symptoms. Drawbacks of tissue sampling include belated detection that is possible only after symptoms appear, necessary slaughter of affected animals, and results that takes days to weeks to complete.        Prionic-Check also requires liquified-brain tissue for use with a novel antibody under the Western Blot technique. This test is as reliable as the immunochemistry technique and is more rapid, yielding results in six to seven hours, but shares the drawbacks of the six-month lag time between PrPS accumulation (responsible for the gross morphology changes) in the brain and the display of clinical symptoms, along with the need for slaughter of the animal to obtain a sample.        Tonsillar Biopsy Sampling. Though quite accurate, it requires surgical intervention and the requisite days to weeks to obtain results.        Body Fluids: Blood and Cerebrospinal Sampling. As in the above detection methods, results are not immediate        Electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance NMR, circular dichroism (CD) and other non-amplified structural techniques. All of these techniques require a large amount of infectious sample, and have the disadvantage of requiring off-site testing or a large financial investment in equipment.        
The difficulty with all of the presently approved tests is that they are time consuming and are performed POST-MORTEM.
As can now be seen, the related art remains subject to significant problems, and the efforts outlined above—although praiseworthy—have left room for considerable refinement. The present invention introduces such refinement.